Modified heparin-based coatings and related drug eluting stents

Abstract

Systems comprising modified heparin-based coatings to form coatings on medical devices are provided. The systems improve the suitability of the heparin-based coatings.

1. An stent comprising:
 a device body having an outer surface; 
 a first coating layer disposed over the outer surface of the device body comprising a hydrophobic polymer; and 
 a second coating layer above the first coating layer, the second coating layer comprising a glycosaminoglycan which is covalently bound to at least one coating material, a second drug which is not a glycosaminoglycan, and either at least one hydrophobic polymer or at least one amphiphile; 
 wherein
 the coating material in the second layer to which the glycosaminoglycan is bound is not the second drug; 
 there are no coating layers above the second coating layer; 
 the second drug in the second coating layer is ionic; and 
 the second coating layer further comprises an ionic component to bind with the second drug, the ionic component being copoly(ethylene glycol-dimethylaminoethyl methacrylate). 
 
 
     
     
       2. The stent of  claim 1 , wherein the glycosaminoglycan is heparin or a heparin-based material. 
     
     
       3. The stent of  claim 1 , wherein the thickness of the first coating layer is between 100 nm and 5 μm. 
     
     
       4. The stent of  claim 1 , wherein the first coating layer further comprises a drug. 
     
     
       5. The stent of  claim 4 , wherein the drug in the first coating layer is micronized heparin or heparin-based material. 
     
     
       6. The stent of  claim 4 , wherein the first coating layer further comprises polyethylene glycol or polyvinylpyrrolidone. 
     
     
       7. The stent of  claim 1 , wherein the second coating layer comprises a hydrophobic polymer selected from the group consisting of poly(ethylene-co-vinyl acetate), poly(ethylene-co-vinyl alcohol), poly(methyl methacrylate), poly(n-butyl methacrylate), poly(methylmethacrylate), poly(vinylidene fluoride) (“PVDF”), poly(vinylidene fluoride-co-hexafluoropropene) (“PDVF-HFP”), poly(tetrafluoroethylene) (“PTFE”), fluorinated poly(ethylene-co-propylene) (“FEP”), poly(hexafluoropropene), poly(chlorotrifluoroethylene) (“PCTFE”), poly(vinylidene fluoride-co-tetrafluoroethylene) (“PVDF-TFE”), poly(tetrafluoroethylene-co-hexafluoropropene), poly(tetrafluoroethylene-co-vinyl alcohol), poly(tetrafluoroethylene-co-vinyl acetate), poly(tetrafluoroethylene-co-propene), poly(hexafluoropropene-co-vinyl alcohol), poly(tetrafluoroethylene-co-fluoromethylvinyl ether), poly(ethylene-co-tetrafluoroethylene) (“ETFE”), poly(ethylene-co-hexafluoropropene), poly(vinylidene fluoride-co-chlorotrifluoroethylene), fluorinated silicones, perfluoroalkyl vinyl ether, tetrafluoroethylene co-polymer (“PFA”), a co-polymer of vinylidenedifluoride, hexafluoropropylene and tetrafluoroethylene (“TFB”), polyvinylfluoride (“PVF”), a copolymer of poly(tetrafluoroethylene) and fluoromethylvinyl ether, poly(vinylidene fluoride-co-chlorotrifluoroethylene), poly(vinylidene fluoride-co-ethylene), poly(vinylidene fluoride-co-tetrafluoroethylene), poly(tetrafluoroethylene-co-ethylene), poly(vinylidene fluoride-co-trifluoroethylene) (“PVDF-TrFE”), poly(vinylidene fluoride-co-tetrafluoroethylene), a poly(ester-amide), a poly(ester-amide) conjugated to heparin, poly(L-lactide), poly(D-lactide), poly(D,L-lactide), poly(meso-lactide), poly(D,L-lactide-block-ethylene glycol-block-D,L-lactide), poly(meso-lactide-block-ethylene glycol-block-meso-lactide), and combinations thereof. 
     
     
       8. The stent of  claim 7 , wherein the second drug in the second coating layer is a rapamycin derivative. 
     
     
       9. The stent of  claim 7 , wherein the second drug in the second coating layer is everolimus. 
     
     
       10. The stent of  claim 1 , wherein the second coating layer comprises an amphiphile, and wherein
 the hydrophobic moiety of the amphiphile is selected from the group consisting of a fluorocarbon, poly(dimethyl siloxane), a long chain alkyl, and combinations thereof and 
 the hydrophilic moiety of the amphiphile is selected from the group consisting of polyethylene glycol, poly(vinyl pyrrolidone), poly(vinyl alcohol), poly(ethylimine), poly(acrylic acid), poly(hydroxy ethyl methacrylate), poly(acrylamide), carboxy methyl cellulose, hyaluronic acid, an oligopeptide, poly(L-lactide), heparin, phosphorylcholine, and combinations thereof. 
 
     
     
       11. The stent of  claim 10 , wherein the second drug in the second coating layer is a rapamycin derivative. 
     
     
       12. The stent of  claim 10 , wherein the second drug in the second coating layer is everolimus.